Proteases and metastasis: clinical relevance nowadays?

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Abstract
A great deal of breast cancer research has been devoted to the search for new prognostic and predictive markers which could, on the one hand, enable a more precise identification of patients at high risk of recurrence and, on the other hand, predict the response of each individual patient to the administered therapy. Proteases have been the center of interest because of their prominent involvement in cancer progression and metastasis. In particular, the matrix metalloproteinases, the serine protease urokinase plasminogen activator, the cathepsins, and corresponding inhibitors have been studied extensively. This article reviews the developments during the last year in this field. The prognostic effect of urokinase plasminogen activator and plasminogen activator inhibitor 1 was confirmed in a meta-analysis and in a prospective randomized clinical study that provided level 1 evidence for the clinical value of these markers. Furthermore, encouraging data suggest that both urokinase plasminogen activator and plasminogen activator inhibitor 1 might be important predictive markers. To date, findings on the prognostic and predictive value of the matrix metalloproteinases, the cathepsins, and their inhibitors are still inconclusive. On the basis of currently available data, tumor urokinase plasminogen activator and plasminogen activator inhibitor 1 levels could already be used in everyday clinical practice for selection of candidates for adjuvant systemic therapy. Further effort should be put into the standardization of the matrix metalloproteinases and cathepsins determination so that their clinical relevance in breast cancer can be defined.

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